Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid ...tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.
•Cancer cells of many tissues express an abnormal glycoform of MUC1, Tn-MUC1•Normal human tissue does not express detectable Tn-MUC1 on the cellular surface•CAR T cells are engineered to target Tn-MUC1 lyse tumor cells in vitro and in vivo•Abnormal glycoform epitopes are valid clinical targets for CAR T cells
Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® ...Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges.
Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018–2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly.
The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.
•Despite best efforts, many of the ERAS recommendations remain poorly adhered to and barriers to ERAS implementation persist.•This guideline update summarizes evidence investigating ERAS implementation challenges highlighted by stakeholder groups.•Overcoming implementation barriers will increase ERAS uptake and improve clinical outcomes for patients.
The 20-item Toronto Alexithymia Scale (TAS-20) is the most widely used instrument for assessing alexithymia, with more than 25 years of research supporting its reliability and validity. The items ...that compose this scale were written to operationalize the components of the construct that are based on clinical observations of patients and thought to reflect deficits in the cognitive processing of emotions. The Perth Alexithymia Questionnaire (PAQ) is a recently introduced measure and is based on a theoretical attention-appraisal model of alexithymia. An important step with any newly developed measure is to evaluate whether it demonstrates incremental validity over existing measures. In this study using a community sample (N = 759), a series of hierarchical regression analyses were conducted that included an array of measures assessing constructs closely associated with alexithymia. Overall, the TAS-20 showed strong associations with these various constructs to which the PAQ was unable to add any meaningful increase in prediction relative to the TAS-20. We conclude that until future studies with clinical samples using several different criterion variables demonstrate incremental validity of the PAQ, the TAS-20 should remain the self-report measure of choice for clinicians and researchers assessing alexithymia, albeit as part of a multi-method approach.
A potential relationship between T cell immunity and development of atrial fibrillation (AF) has been proposed. Historically in AF patients it has been reported that peripheral blood had elevated ...CD4+ T cells. However few studies have explored whether there is a direct increase of CD4+ T cells in atrial tissues with AF. In this study, public domain micro-array dataset of cardiac surgery patients with atrial tissue biopsies in AF and non-AF patients have been used to explore immune cell subsets. Machine learning based deconvolution of permanent atrial fibrillation microarray atrial samples was applied using Cibersort to enumerate the relative fractions of twenty-two different leukocyte sub-populations. Cibersort enumerated significantly increased fractions of follicular CD4+ T lymphocytes and gamma-delta T cells in the atria of permanent AF subjects. Gene expression analysis of permanent AF microarray tissue samples with elevated follicular CD4+ T cell fractions with gene pathways associated with myocardial substrate remodelling. That is both integrin and non-integrin mediated gene interactions between inflammatory cells and the extra cellular matrix, including infiltrating follicular CD4+ T cells that trafficked to the atria by virtue of the repertoire of cell surfaced expressed adhesion molecules. Additionally, IL-17 and other interleukin inflammatory gene heat maps were associated with enhanced CD4+ follicular T cell expression in our profiled atrial tissues with AF. These observations suggest that atrial structural remodelling was associated with the presence of pathogenic T cell mediated inflammation, present in AF atria but not in non-AF atria.
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Gold nanoparticles having a rod-like morphology are regularly investigated as potential nano-therapeutic materials owing to their interesting optical properties, facile surface ...modification, tunable aspect ratios, and low cytotoxicity. Gold nanorods are historically prepared starting from HAuCl4 in the presence of ascorbic acid, silver nitrate, and the growth directing surfactant, cetyltrimethylammonium bromide (CTAB). While CTAB drives a rod-like morphology, it is known to be cytotoxic. This inherent toxicity is often addressed by removing or masking the native CTAB surfactant present on the nanorod surface. In the current study we have investigated a less toxic alternative surfactant, dodecylethyldimethylammonium bromide (C12EDMAB), as a possible growth-directing agent. Monodisperse gold nanorods having various lengths have been grown in the presence of C12EDMAB. SEM data suggests that the quantity of C12EDMAB on the rod’s surface is much higher than that of CTAB. Toxicity assays were performed on HEp-2 and A549 cells showing lower toxicity at select concentrations for C12EDMAB coated rods.
Improvements to tapered photonic crystal fiber (PCF) fabrication have allowed us to make up to 50 m long PCF tapers with loss as low as 30 dB/km. We discuss the design constraints for tapered PCFs ...used for adiabatic soliton compression and demonstrate over 15 times compression of pulses from over 830 fs to 55 fs duration at a wavelength of 1.06 lm, an order of magnitude improvement over previous results.
Stress fractures, including both fatigue and insufficiency types, are frequently encountered in clinical practice as a source of pain in both athletes and patients with predisposing conditions. ...Radiography is the imaging modality of choice for baseline diagnosis. MRI has greatly improved our ability to diagnose radiographically occult stress fractures. Tc-99m bone scan and CT may also be useful as diagnostic tools. Although fatigue and insufficiency fractures can be self-limited and go onto healing even without diagnosis, there is usually value in initiating prompt therapeutic measures as incomplete stress fractures have the potential of progressing to completion and requiring more invasive treatment or delay in return to activity. This is particularly important in the setting of stress fractures of the femoral neck. Accuracy in the identification of these injuries is also relevant because the differential diagnosis includes entities that would otherwise be treated significantly different (ie, osteoid osteoma, osteomyelitis, and metastasis). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures ...of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.
This retrospective study evaluated the technical success rate of a novel injection into the long head of the biceps tendon sheath by a rotator interval approach in 26 patients. A 25‐gauge, 1.5‐in ...needle was positioned into the rotator interval from a lateral approach, where a therapeutic injection was performed. Postinjection sonograms images were reviewed to assess for fluid within the sheath to calculate the technical success rate. Fluid distention of the biceps tendon sheath was shown in all 26 cases, corresponding to a 100% technical success rate. In addition, postinjection ultrasound imaging of the anterior shoulder provided additional diagnostic findings in 6 of 26 patients (23%).
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